The aim of the proposed studies is to gain a better understanding of the influence of nerve upon the "fast" (twitch) extensor digitorum longus and "slow" (tonic) soleus muscles of the rat and of the alterations which occur when such influence is suppressed and subsequently re-established. An electrophysiological, pharmacological and ultrastructural investigation of the alterations which occur in the "fast" posterior latissimus dorsi and "slow" anterior latissimus dorsi of chickens with inherited muscular dystrophy will also be carried out. Intracellular, extracellular, current clamp and electron microscpe techniques will be used. The project has the following objectives: 1) To continue the electrophysiological and pharmacological studies of the denervated, reinnervated and cross-innervated mammalian muscles in order to characterize the influence of nerve upon muscle; 2) to determine the specific alterations in the sodium and potassium conductances of the end-plate potentials which occur in the "fast" and "slow" muscle during the first few days of reinnervations; 3) to study the presynaptic actions of batrachotoxin and histrionicotoxin and their analogs in normal and reinnervated muscles of the rat; 4) to investigate the appearance of fibrillation potentials and tetrodotoxin-resistant action potentials in denervated muscles and its correlation with neurotrophic influence; 5) to determine the effects of chronic application of selected local anesthetics and antimitotic drugs on sciatic nerves of the rat; 6) to study the actions of histrionicotoxin, perphydrohistrionicotoxin and alpha bungarotoxin on the acetylcholine- receptor of the denervated muscles; 7) To provide quantitative information on the electrophysiological characteristics of the "normal", denervated and reinnervated dystrophic muscles; 8) to determine the mechanism of the atrophy which occurs in the "fast" dystrophic muscles; 9) to compare the quantal content, available store of transmitter and equilibrium potential of the end-plate potentials of normal vs. dystrophic; 10) to assess the efficacy of batrachotoxin and its analogs and other compounds which increase sodium conductance in reversing the dystrophic condition.